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. 2016 Mar 10;3(3):e1134411.
doi: 10.1080/23723556.2015.1134411. eCollection 2016 May.

A TAD closer to ATM

Francois Aymard  1 , Gaëlle Legube  1
Affiliations

A TAD closer to ATM

Francois Aymard et al. Mol Cell Oncol. .

Abstract

Ataxia telangiectasia mutated (ATM) has been known for decades as the main kinase mediating the DNA double-strand break response. Our recent findings suggest that its major role at the sites of breaks likely resides in its ability to modify both the local chromatin landscape and the global chromosome organization in order to promote repair accuracy.

Keywords: ATM; DNA double-strand break; chromatin; clustering; cohesin; topologically associated domains; γH2AX.

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Figures

Figure 1.
Figure 1.
ATM-mediated H2 AX phosphorylation and DSB clustering. Upon damage detection, ataxia telangiectasia mutated (ATM) is recruited to a restricted region surrounding the double-strand break (DSB). H2AX-containing nucleosomes present within the damaged topologically associated domain (TAD, in red) are then phosphorylated, possibly as a result of local chromatin mobility that brings nucleosomes into the spatial vicinity of ATM. This leads to spreading of γH2AX through the entire damaged TAD. ATM may also phosphorylate other chromatin substrate(s) (in yellow) to locally enhance the mobility. This enhanced mobility could lead to increased H2AX phosphorylation within the TAD and favor DSB clustering.
See this image and copyright information in PMC

References

    1. Caron P, Choudjaye J, Clouaire T, Bugler B, Daburon V, Aguirrebengoa M, Mangeat T, Iacovoni JS, Alvarez-Quilon A, Cortes-Ledesma F, et al. . Non-redundant functions of ATM and DNA-PKcs in response to DNA double-strand breaks. Cell Rep 2015; 13:1598–609; PMID:26586426; http://dx.doi.org/10.1016/j.celrep.2015.10.024 - DOI - PMC - PubMed
    1. Caron P, Aymard F, Iacovoni JS, Briois S, Canitrot Y, Bugler B, Massip L, Losada A, Legube G. Cohesin protects genes against gammaH2AX Induced by DNA double-strand breaks. PLoS Genet 2012; 8:e1002460; PMID:22275873; http://dx.doi.org/10.1371/journal.pgen.1002460 - DOI - PMC - PubMed
    1. Lee CS, Lee K, Legube G, Haber JE. Dynamics of yeast histone H2A and H2B phosphorylation in response to a double-strand break. Nat Struct Mol Biol 2014; 21:103–9; PMID:24336221; http://dx.doi.org/10.1038/nsmb.2737 - DOI - PMC - PubMed
    1. Becker A, Durante M, Taucher-Scholz G, Jakob B. ATM alters the otherwise robust chromatin mobility at sites of DNA double-strand breaks (DSBs) in human cells. PLoS One 2014; 9:e92640; PMID:24651490; http://dx.doi.org/10.1371/journal.pone.0092640 - DOI - PMC - PubMed
    1. Goodarzi AA, Jeggo P, Lobrich M. The influence of heterochromatin on DNA double strand break repair: Getting the strong, silent type to relax. DNA Repair (Amst) 2010; 9:1273–82; PMID:21036673; http://dx.doi.org/10.1016/j.dnarep.2010.09.013 - DOI - PubMed

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